Researchers discover a novel therapy for chronic pain by blocking an intracellular protein interaction in the central nervous system



    TORONTO, Nov. 16 /CNW/ - Researchers at The Hospital for Sick Children
(SickKids) and the University of Toronto have developed a novel peptide for
treating pain by blocking an intracellular protein interaction in the central
nervous system. This research is reported online on November 16 in the journal
Nature Medicine.
    This research was made possible with the support of a $1.75-million
NeuroScience Canada Brain Repair Program team grant that enabled Dr. Michael
Salter and his team to join with other scientists from across Canada to work
together and fast track their research.
    "A major roadblock in chronic pain research has been translating
knowledge of biological mechanisms into therapeutic approaches that are both
effective and safe," said Dr. Salter, the study's principal investigator,
Senior Scientist and Head of the Program in Neurosciences and Mental Health at
SickKids, Professor of Physiology and Director of the University of Toronto
Centre for the Study of Pain, International Research Scholar of the Howard
Hughes Medical Institute and holder of a Canada Research Chair. "We were able
to move past it with our discovery of a novel peptide-based therapeutic
approach, which may lead to a new and previously unsuspected way of treating
chronic pain."
    Chronic pain hypersensitivity is known to involve N-methyl-D-aspartate
receptors (NMDARs), a main type of receptor mediating communication between
nerve cells in the brain and spinal cord. However, treating chronic pain
through the use of NMDAR blocking drugs is limited because NMDARs are
essential for many key physiological functions, including breathing and
cognition. Salter's team discovered that pain hypersensitivity depends upon
amplification of the function of NMDARs by an enzyme known as Src.
    Using mouse models, the team designed a peptide that is able to prevent
the action of Src to amplify NMDAR function. This was achieved by designing
the peptide to disrupt the interaction between two proteins, Src and NADH
dehydrogenase subunit 2 (ND2), which anchors Src to NMDAR. Salter's team shows
that the peptide selectively inhibits the amplification of NMDAR that produces
chronic pain, without affecting psychological functions of the receptor.
    "The peptide has key characteristics of an ideal analgesic in reducing
pain in models of both chronic inflammatory and neuropathic pain, the two main
types of chronic pain," says Dr. Xue Jun Liu, the study's lead author, a
post-doctoral fellow at SickKids and the University of Toronto. "This is
critical because it can be difficult to distinguish inflammatory versus
neuropathic pain, as patients often have symptoms of both types, and presently
available analgesics may only be effective against one type or the other."
    Chronic pain is a pervasive, insidious and often devastating problem that
affects both children and adults. According to the Canadian Pain Survey, one
in six Canadians (16 per cent) live with constant pain, and one in five (20
per cent) experience pain daily. The total annual economic cost of pain is
estimated to be $40 billion in Canada alone. However, the impact of chronic
pain should not be viewed simply in economic terms. Chronic pain has a major
detrimental effect on the quality of life of the millions of chronic pain
sufferers and their families worldwide.
    Other members of the research team were Jeffrey R. Gingrich, Mariana
Vargas-Caballero, Yi Na Dong, Ameet Sengar, Simon Beggs, Szu-Han Wang, Hoi Ki
Ding and Paul W. Frankland, all from SickKids.
    This research was also supported by the Canadian Institutes of Health
Research, the Ontario Neurotrauma Foundation, the Krembil Foundation, and
SickKids Foundation.

    Founded in 1998, NeuroScience Canada (NSC) is a national non-profit
organization that develops and supports collaborative, multidisciplinary,
multi-institutional research across the neurosciences. Through partnering with
the public, private and voluntary sectors, NeuroScience Canada connects the
knowledge and resources available in this area to maximize the output of
Canada's world-class scientists and researchers.
    The mission of NeuroScience Canada's Brain Repair Program(TM) is to
accelerate "transformative" research to discovery and to the development of
new treatments and therapies for neurological and psychiatric diseases and
disorders. NSC is achieving this by funding teams of investigators from
various disciplines and institutions that have the best chance of producing
rapid progress in repairing the brain. In the first phase of the Brain Repair
Program, NSC and its donors and partners are investing $8 million in research
teams.

    Salter is the lead investigator of the Brain Repair Program project
titled, Transforming research on chronic pain in Canada. NeuroScience Canada
has invested $1.75 million in this project for this team to conduct
breakthrough work in the area of neuroscience.

    The Hospital for Sick Children (SickKids), affiliated with the University
of Toronto, is Canada's most research-intensive hospital and the largest
centre dedicated to improving children's health in the country. As innovators
in child health, SickKids improves the health of children by integrating care,
research and teaching. Our mission is to provide the best in complex and
specialized care by creating scientific and clinical advancements, sharing our
knowledge and expertise and championing the development of an accessible,
comprehensive and sustainable child health system. For more information,
please visit www.sickkids.ca. SickKids is committed to healthier children for
a better world.





For further information:

For further information: Lisa Lipkin, Public Affairs, Tel: (416)
813-6380, e-mail: lisa.lipkin@sickkids.ca

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